This invention relates to intermediates useful in the preparation of prostaglandins and analogs, and to a process for preparing them.
The prostaglandins and analogs are well-known organic compounds derived from prostanoic acid which has the following structure and atom numbering: ##STR2## Among the prostaglandins are prostaglandin F.sub.2.alpha., "PGF.sub.2.alpha. ", and prostaglandin F.sub.3.alpha., "PGF.sub.3.alpha. ", which are represented by formulas II and III, respectively: ##STR3##
The prostaglandin formulas mentioned above each have several centers of asymmetry. As drawn, each formula represents the particular optically active form of the prostaglandin obtained from certain mammalian tissues, for example, sheep vesicular glands, swine lung, and human seminal plasma, or by reduction or dehydration of a prostaglandin so obtained. See, for example, Bergstrom et al., Pharmacol. Rev. 20, 1 (1968), and references cited therein. The mirror image of each formula represents a molecule of the enantiomer of that prostaglandin. The racemic form of the prostaglandin consists of equal numbers of two types of molecules, one represented by one of the above formulas and the other represented by the mirror image of that formula. Thus, both formulas are needed to define a racemic prostaglandin. See Nature 212, 38 (1966) for discussion of the stereochemistry of the prostaglandins. For convenience hereinafter, use of the terms "PGF.sub.2.alpha. ", "PGF.sub.3.alpha. ", and the like, will mean the optically active form of that prostaglandin with the same absolute configuration as PGE.sub.1 obtained from mammalian tissues.
In the formulas given above, as well as in the formulas given hereinafter, broken line attachments to the cyclopentane ring indicate substituents in alpha configuration, i.e., below the plane of the cyclopentane ring. Heavy solid line attachments to the cyclopentane ring indicate substituents in beta configuration, i.e., above the plane of the cyclopentane ring.
Prostaglandins F.sub.2.alpha. and F.sub.3.alpha. are well known in the art, including methods of preparation and demonstrations of utility. See, for example, U.S. Pat. Nos. 3,706,789 and 3,804,879; Bergstrom et al., Pharmacol. Rev. 20, 1 (1968) and references cited therein; and E. J. Corey et al., J. Am. Chem. Soc. 92, 397 (1970) and 93, 1490 (1971).
One illustration of a prostaglandin analog is 16,16-dimethyl-PGF.sub.2.alpha., represented by formula IV: ##STR4## For background of this compound, see, for example, U.S. Pat. No. 3,903,131.
Also representative of prostaglandin analogs are 15-methyl- and 15-ethyl-PGF.sub.2.alpha., represented by formula V: ##STR5## wherein R.sub.11 is methyl or ethyl. For background on these compounds, see, for example, U.S. Pat. No. 3,728,382.
Still another illustration of a prostaglandin analog is 4,5-didehydro-PGF.sub.1.alpha., represented by formula VI: ##STR6## For background on this compound, see, for example, German Offenlegungsschrift No. 2,320,552.9, or the abstract in Derwent Farmdoc No. 69674U.